甲胎蛋白基因多态性与 HCC 和肝硬化的风险。

Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis.

机构信息

Mochtar Riady Institute for Nanotechnology, Lippo Karawaci, Tangerang, Indonesia.

出版信息

Clin Chim Acta. 2010 Mar;411(5-6):351-8. doi: 10.1016/j.cca.2009.11.030. Epub 2009 Dec 5.

DOI:10.1016/j.cca.2009.11.030

PMID:19968979

Abstract

BACKGROUND

Elevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians.

METHODS

Direct DNA sequencing was carried out to sequence AFP promoter, exons, and 3' untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.

RESULTS

In this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3'UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis.

CONCLUSION

Genetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.

摘要

背景

约 60%的肝细胞癌 (HCC) 病例中发现甲胎蛋白 (AFP) 水平升高。其他肝脏疾病，包括肝硬化和慢性肝炎，与 AFP 水平升高有关。尽管该基因被认为在 HCC 发展中起作用，但 AFP 基因表达的调控相对研究较少。本研究旨在确定 AFP 中的遗传变异，这些变异可能与印度尼西亚人群中 HCC 和肝硬化的存在有关。

方法

对从 119 例 HCC、119 例肝硬化和 105 例对照中分离的 DNA 样本进行 AFP 启动子、外显子和 3'非翻译区 (UTR) 的直接 DNA 测序。对每个样本的血清 AFP 水平进行测定，并对单核苷酸多态性 (SNP) 和单倍型与 HCC 和肝硬化的关联进行了研究。

结果

本研究在 AFP 基因中鉴定出 47 个 SNPs。在 AFP 启动子、AFP 内含子 1 和内含子 2 中发现了 6 个个体 SNP 与 HCC 和肝硬化有统计学显著关联(rs6834059、rs3796678、rs3796677、rs3796676、rs28532518 和 rs4646038)。此外，我们还在 AFP 内含子 7 和 3'UTR 中发现了两个与肝硬化风险增加相关的 SNPs(rs2298839 和 rs10020432)。